Headache Currents
HEADACHE CURRENTS—CLINICAL REVIEW
Idiopathic Intracranial Hypertension: Pseudotumor Cerebri Gregory S. Kosmorsky, DO
Background.—Idiopathic intracranial hypertension (IIH) is most often diagnosed in young obese females of childbearing years. The diagnosis is made based on the modified Dandy criteria and the exclusion of alternate causes of raised intracranial pressure. Results.—The focus of this review is to provide an overview of the diagnosis and treatment options for patients with IIH. There are long-term consequences for patients experiencing IIH, with visual loss being the most serious. Conclusion.—We conclude that the diagnosis of IIH is not usually difficult. An ophthalmologic examination is essential in patients with IIH to monitor visual function. A neurologist or neurosurgeon may be needed at some point for medical and/or surgical intervention. Key words: idiopathic intracranial hypertension, pseudotumor cerebri, cerebrospinal fluid, increased cerebrospinal fluid pressure, Dandy criteria
Idiopathic intracranial hypertension (IIH) is a disorder generally affecting overweight women of childbearing years.1-4 The pathogenesis is unknown, but ultimately, a defect in water absorption seems to be the common feature. Although it is believed that this absorptive problem occurs at the level of the arachnoid,5 recent insights into the water balance of the brain challenge this contention.6 The diagnosis is based on clinical symptomatology and findings, normal imaging studies, an elevated opening pressure on lumbar puncture with a normal cerebrospinal fluid (CSF) constituency, and elimination of systemic disorders that mimic the typical profile.7 The modified Dandy criteria serve as the basis for the diagnosis and include: (1) symptoms and signs of increased intracranial pressure (ICP); (2) no localizing neurologic signs, except for unilateral or bilateral sixth nerve palsies; (3) increased CSF opening pressure, but normal CSF constituency; (4) no evidence of hydrocephalus, mass, structural, or vascular lesion on imaging; and (5) no other cause of increased ICP identified.8
IIH Clinical Characteristics The patient profile in IIH is quite striking and characteristic. Overwhelmingly, this is a disorder of overweight females of From the Cole Eye Institute, Cleveland, OH, USA. Address all correspondence to Gregory S. Kosmorsky, Cleveland Clinic Foundation, Cole Eye Institute, Cleveland Clinic I-30, Cleveland, OH 44195, USA. Accepted for publication October 25, 2013. ............. Headache © 2014 American Headache Society
childbearing years. It is the most skewed non-sex organ–related disorder, with a female to male ratio of 9:1.3 The most common manifestation of IIH is headache. This has been reported in 75-99% of patients. The headache is non-specific and is usually holocranial although it can be vertex or suboccipital. Similar to all headaches due to elevated ICP, it may be worse upon awakening and increased with the Valsalva maneuver. It should be noted that as many as 10% of patients with IIH are entirely asymptomatic from a headache perspective.9,10 The headache can be severe and does seem to negatively impact quality-of-life indicators as measured by the HRQOL score.3 Monocular and binocular transient visual obscurations (TVOs) are momentary blackouts of vision most likely due to temporary disruption in the microcirculation of the optic nerve head induced by transient changes in perfusion pressure at the level of the optic nerve usually associated with postural changes. Many TVOs occur with a postural change, although some may occur while the patient sits quietly. TVOs are not predictive of permanent visual loss and can disappear with or without a reduction in CSF pressure.1,11 They are not unique to IIH and have been shown to occur with any disorder that produces swelling of the optic nerve head. Sadun et al have demonstrated that TVOs may occur in patients with elevated optic discs from causes not related to increased ICP.12 They postulate that these visual obscurations appear to be due to transient ischemia of the optic nerve head consequent to increased tissue pressure within the optic nerve. They further postulate that axonal swelling, intraneural masses, and increased influx of interstitial fluid may all contribute to increases in tissue pressure in the optic nerve head, consequently reducing the perfusion pressure in the small, low-pressure vessels that supply the optic nerve. Even disorders such as myopia and optic nerve drusen have produced TVOs. Evaluation and Workup The evaluation of IIH includes the history, physical examination, blood work, imaging studies, and a lumbar puncture. The history and physical should suggest raised ICP. Mimickers such as cerebral venous thrombosis, gliomatosis cerebri, and leptomeningeal infiltration by neoplastic or infectious processes need to be considered. A complete blood count (CBC) and general chemistry analysis should be obtained to exclude anemia or lymphoproliferative causes. The general chemistry can be used to detect renal disease that can complicate this condition especially in African American males.13 Iron deficiency can be reflected in the CBC; therefore, iron studies could be ordered when indicated. ............. The author has no conflicts to disclose.
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Imaging studies are mandatory and the MRI is the preferred modality given its ability to not only detects mass lesions and hydrocephalus, but also to detect venous sinus thrombosis and potentially a meningeal process. A lumbar puncture is required to establish the level of CSF pressure and to examine the CSF constituency.14,15 Red flags in the diagnosis of IIH include: (1) atypical demographic profile; (2) cranial nerve palsies other than a 6th nerve palsy; (3) alterations in level of consciousness; (4) focal neurologic sings apart from a 6th nerve palsy; (5) abnormal CSF profile; (6) explosive onset of symptoms; (7) rapid development of visual loss and progression of symptoms; (8) global ophthalmoplegia; (9) internuclear ophthalmoplegia; and (10) vertical gaze disorder.14 Further Clinical Features in Considering the Diagnosis Diplopia occurs almost exclusively from 6th nerve palsies16 that may be unilateral or bilateral and are non-localizing. There are rare reports of skew deviation,17 4th nerve palsies,18,19 and even 3rd nerve palsies in IIH;20,21 however, these occurrences are exceptional, and the diagnosis was not firm in some of these patients. Any diplopia not due to a 6th nerve palsy should make the diagnosis of IIH suspect. Facial paresis and facial pain have occasionally been reported in IIH.22-26 These are extremely unusual features, and mass lesions should be ruled out in these patients. Pulsatile tinnitus due to elevated ICP is most likely the result of turbulent blood flow at the level of the jugular bulb during diastole wherein elevated CSF pressure causes these draining veins to vibrate.27-29 Tinnitus due to elevated ICP can be differentiated from tinnitus due to other causes by reducing CSF pressure via a lumbar puncture or compression of the internal jugular vein that prevents the jugular vein from vibrating during diastole. Low back pain and radiating paresthesias are thought to be due to dilation of nerve root sleeves secondary to increased ICP.30 Paresthesias in IIH have been reported in all extremities and without demonstrable sensory abnormalities. Aching legs can be a complaint with IIH and may be attributed to pressure on the lumbar roots at the level of the dural sleeve.31,32 Arthralgia coincided with high-pressure plateau waves during continuous ICP monitoring in a patient with “high pressure normocephalus.” This patient had episodic pain of the shoulders, knees, and hips, with headache as a minor complaint.30 Momentary ataxia occurred in four patients in the report of Round and Keane, who suggested that this may be due to brief hypoperfusion of the brain stem.30 Papilledema in IIH is no different from papilledema in any other condition related to increased ICP. Swelling of the nerve fiber layer occurs, with hemorrhages in the nerve fiber layer or in the subretinal space being frequently seen. Lipoproteinaceous exudates within the retina, as well as cotton-wool spots from infarction of the nerve fiber layer, may be
Headache Currents seen, but these other features may suggest other disorders, particularly vasculitis. Loss of venous pulsations is typical with increasing ICP, although spontaneous venous pulsations may be seen in patients with papilledema, indicating that the ICP at that time may in fact be normal or that SVPs may still be present with increased ICP in some patients.33-36 There is no direct correlation of the presence of venous pulsations and level of ICP. Predominantly unilateral or strictly unilateral optic nerve swelling has occasionally been reported.37 The presence of highly asymmetric or strictly unilateral papilledema should not dissuade a physician from making the diagnosis of IIH. Asymmetric papilledema is thought to be due to differences in individual optic nerve anatomy as shown by Hayreh et al.38-42 Hayreh demonstrated in pathologic specimens that some individuals have a tighter subarachnoid space within the optic canal, thereby preventing raised ICP from accessing the posterior globe at the lamina cribrosa, where either mechanical and/or ischemic factors seem to produce papilledema. Such a patient was described by Maxner et al in whom unilateral papilledema in the left eye led to an initial diagnosis of anterior ischemic optic neuropathy.43 Gradual progression of visual field loss prompted reassessment, with the eventual diagnosis of IIH being confirmed. Even more unusual is the absence of papilledema with raised ICP.44 Such cases are considered rare; however, because clinicians do not routinely do lumbar punctures on patients without papilledema, the true incidence of this presentation is likely underestimated. In patients diagnosed with chronic daily headache (without papilledema), the proportion of patients with IIH seems to be higher.45 Although most patients present with mild to moderate grades of papilledema, there are those who present with a very aggressive form of IIH with severe papilledema and profound visual loss. These patients require aggressive treatment and my approach is to try medications (acetazolamide and burst and taper methylprednisolone) for a short period of time (1-2 weeks), and if the visual loss is not quickly reversed, I proceed to optic nerve sheath fenestration or refer to neurosurgery for a ventriculoperitoneal shunt. It is impossible to ascertain how long papilledema has been present merely by fundus appearance. Papilledema of long standing may appear to be quite new, with hyperemia of the disc and telangiectatic-like dilation of the capillaries on the surface of the disc. However, if optic atrophy, gliosis, optociliary shunts, and pseudodrusen (tiny reflectile particles in the nerve fiber layer) are seen, chronicity may be implied, although the exact length of time is impossible to ascertain. Papilledema may resolve with little or no residuum. Consequences of sustained increases of ICP include optic atrophy with or without significant visual loss, optociliary shunt vessels, chorioretinal folds, subretinal hemorrhages, macular
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edema, peripapillary choroidal neovascular membranes, and nerve fiber layer defects with visual field loss.46-50 Chronic papilledema may also cause arterial or venous occlusions (either total or partial), presumably on the basis of mechanical distortion of the arteries or veins. Long-Term Consequences of IIH Visual field abnormalities in IIH are common and occur in approximately 50% of patients.49,51 Serious unilateral or bilateral visual loss has been reported in up to 25% of patients. It is generally agreed that visual loss is the only serious complication of IIH. The most common visual field defect is an enlarged blind spot that has been shown to be secondary to a refractive scotoma, presumably due to displacement of the peripapillary rods and cones by swollen axons.43 Because blind spot enlargement may persist after papilledema disappears and because other conditions mimicking papilledema, such as drusen, can also enlarge the blind spot, plotting the blind spot is an unreliable measure of therapeutic success and an inaccurate way of observing a patient’s visual function. Rather, arcuate or altitudinal defects that indicate affectation of the nerve fiber layer are more consequential and indicative of optic nerve dysfunction. As with glaucoma, central acuity is lost last in papilledema, and assessment of the visual field with formal testing is mandatory in this disorder to assure proper function of the optic nerve. Generalized constriction of the visual field may be seen in papilledema and indicates severe loss of the nerve fiber layer. However, this is a non-specific sign and may be seen with abnormalities of the cornea or lens or simply with inattention during the testing process, as well as many other factors. Nerve fiber layer defects are common in IIH. These are usually arcuate scotomas in the nasal region and may be either inferior or superior and identical to those field defects seen in any type of optic neuropathy. Even altitudinal visual field-shaped defects or temporal visual field defects can be seen. Central visual field loss is not common but may occur with involvement of the papillomacular bundle and as noted above, usually a late finding. Central visual field loss may also result from subretinal hemorrhage within the papillomacular bundle or macula, secondary to significant papilledema. Assessment of the nerve fiber layer has been greatly enhanced with the use of ocular coherence tomography (OCT) that can reliable measure the thickness of the retina and give a repeatable and statistically valid representation of the degree of injury to the optic nerve.52,53 OCT may be used to differentiate swelling from raised ICP from ischemic optic neuropathy.54 Since patients with functional disease present to the clinician, we should be wary of patients claiming severe visual loss in the absence of papilledema or optic atrophy. The pathophysiology of the visual loss requires the optic disc to be swollen, as the axons of the optic nerve cannot be damaged by raised ICP anywhere
Headache Currents except at the neuro-ocular junction (in the same way that the neurons of the brain tolerate the raised ICP without becoming edematous). The relative afferent pupillary defect (RAPD) is an objective sign of anterior visual pathway dysfunction. Papilledema may cause temporary or permanent dysfunction of visual axons. If this damage is asymmetric, the RAPD will become apparent clinically. Symmetric dysfunction will not produce an RAPD, despite significant visual loss. The finding of an RAPD is extremely important because it indicates the need for intervention in a patient with IIH. Management of IIH Treatment of the visual aspects of IIH depends on the severity of the disorder. Since many patients have little if any visual field loss, no particular therapy is required in the face of a normal visual field. Headache in the setting of a normal visual field may represent a sufficient reason for treatment. In those patients with significant initial field loss, or particularly in those with progressive visual field loss, treatment with medications that lower ICP is indicated. Acetazolamide has been demonstrated to be the most potent medication for lowering ICP.8,55 The usual dosage is either 500 mg sequels bid or 250 mg tablets qid. The branded DIAMOX sequels are significantly more expensive than the generic tablet form. Other sulfa-containing compounds such as furosemide and topiramate may also be used, as drugs in this class all interfere with carbonic anhydrase and reduce the amount of CSF that is made, bringing CSF production into line with reduced CSF drainage. Topiramate has the added advantage of blocking the upregulation of pain signaling and therefore can address both the CSF production and headache aspects.55-57 Weight loss of as little as 6% of body weight has been shown to reduce papilledema, and this form of therapy should be encouraged.58 Pulsed corticosteroids have been demonstrated to have an ameliorating effect, but long-term use of steroids should be avoided.59 A controversial approach is to employ venous stenting procedures to reduce the ICP. Narrowing of the draining veins has been proposed as a mechanism of raised ICP, but it may be that the elevation of ICP causes the narrowing.60 If medications and weight loss fail, some form of CSF diversion procedure would be indicated. The neurosurgical approach usually involves either and lumboperitoneal shunt or ventriculoperitoneal shunt, but other procedures have been described.11,61 From an ophthalmic perspective, optic nerve sheath decompression (ONSD) is the primary procedure.62-67 This procedure may be performed from either the medial, lateral, or superior approach. I prefer the medial approach because it is rapid and
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opens the dura/arachnoid complex on the nasal side avoiding the papillomacular bundle that is temporally situated, if the knife were to penetrate too deeply with the lateral approach. The superior approach is preferred by some ophthalmic plastic surgeons, but the majority of surgeons performing ONSD prefer the medial approach. The purpose of the procedure is to divert elevated CSF pressure that is transmitted from the CSF compartment to the neuroocular junction via the subarachnoid space of the optic nerve that is continuous with the CSF compartment. The CSF then leaks into the periorbital fat via the formation of a filtration bleb and is absorbed by the veins in the fat. Although ONSD can be very effective, it can result in a range of complications.68
SUMMARY The diagnosis of IIH is usually not difficult. Provided that the history, examination, neuroimaging studies, and lumbar puncture are all consistent with IIH, the diagnosis can be made easily. The elimination of look-alikes should be complete with appropriate testing. After the diagnosis is made, patients should be observed closely in terms of their visual field and visual acuity until it is apparent that these are stable. Patients who have progressive loss of visual acuity or visual field should be treated promptly. An ophthalmologist should be involved in the care of these patients along with a neurologist or neurosurgeon because visual loss may occur either early or late in the disease process and may be insidious. The most effective treatments are weight loss, carbonic anhydrase inhibitors, and diuretics, and, if necessary, a short course of steroids. If visual loss occurs despite these maneuvers, some type of shunt procedure is recommended. There seems to be no reason to treat the asymptomatic patient with IIH. References 1. Corbett J. Idiopathic intracranial hypertension. J Neuroophthalmol. 2012;32:e4-e6. 2. Corbett JJ. The 1982 silversides lecture. Problems in the diagnosis and treatment of pseudotumor cerebri. Can J Neurol Sci. 1983;10: 221-229. 3. Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007;143:635-641. 4. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988;45:875-877. 5. Johnston I, Paterson A. Benign intracranial hypertension. II. CSF pressure and circulation. Brain. 1974;97:301-312. 6. Oreskovic D, Klarica M. The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Res Rev. 2010;64:241-262. 7. Friedman DI. Idiopathic intracranial hypertension with Dan and beyond: The 2010 Jacobson Lecture. J Neuroophthalmol. 2010;30: 380-385.
Headache Currents 8. Thurtell MJ, Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri): Recognition, treatment, and ongoing management. Curr Treat Options Neurol. 2013;15:1-12. 9. Strominger MB, Weiss GB, Mehler MF. Asymptomatic unilateral papilledema in pseudotumor cerebri. J Clin Neuroophthalmol. 1992;12:238-241. 10. Weig SG. Asymptomatic idiopathic intracranial hypertension in young children. J Child Neurol. 2002;17:239-241. 11. Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol. 1989;46:1049-1051. 12. Sadun AA, Currie JN, Lessell S. Transient visual obscurations with elevated optic discs. Ann Neurol. 1984;16:489-494. 13. Corbett JJ. Increased intracranial pressure: Idiopathic and otherwise. J Neuroophthalmol. 2004;24:103-105. 14. Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. 2004;24:138-145. 15. Kosmorsky G. Pseudotumor cerebri. Neurosurg Clin N Am. 2001;12:775-797, ix. 16. Bruce BB, Newman NJ, Biousse V. Ophthalmoparesis in idiopathic intracranial hypertension. Am J Ophthalmol. 2006;142:878-880. 17. Baker RS, Buncic JR. Vertical ocular motility disturbance in pseudotumor cerebri. J Clin Neuroophthalmol. 1985;5:41-44. 18. Lee AG. Fourth nerve palsy in pseudotumor cerebri. Strabismus. 1995;3:57-59. 19. Speer C, Pearlman J, Phillips PH, Cooney M, Repka MX. Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri. Am J Ophthalmol. 1999;127:236-237. 20. Tan H. Bilateral oculomotor palsy secondary to pseudotumor cerebri. Pediatr Neurol. 2010;42:141-142. 21. Thapa R, Mukherjee S. Transient bilateral oculomotor palsy in pseudotumor cerebri. J Child Neurol. 2008;23:580-581. 22. Bakshi SK, Oak JL, Chawla KP, Kulkarni SD, Apte N. Facial nerve involvement in pseudotumor cerebri. J Postgrad Med. 1992;38:144145. 23. Kearsey C, Fernando P, Benamer HT, Buch H. Seventh nerve palsy as a false localizing sign in benign intracranial hypertension. J R Soc Med. 2010;103:412-414. 24. Capobianco DJ, Brazis PW, Cheshire WP. Idiopathic intracranial hypertension and seventh nerve palsy. Headache. 1997;37:286288. 25. Chutorian AM, Gold AP, Braun CW. Benign intracranial hypertension and Bell’s palsy. N Engl J Med. 1977;296:1214-1215. 26. Kiwak KJ, Levine SE. Benign intracranial hypertension and facial diplegia. Arch Neurol. 1984;41:787-788. 27. Lee AG. Pulsatile tinnitus as a presenting symptom of pseudotumour cerebri. J Otolaryngol. 1996;25:203-204. 28. Sismanis A. Otologic manifestations of benign intracranial hypertension syndrome: Diagnosis and management. Laryngoscope. 1987;97(8 Pt 2 Suppl. 42):1-17. 29. Sismanis A. Pulsatile tinnitus. A 15-year experience. Am J Otol. 1998;19:472-477. 30. Round R, Keane JR. The minor symptoms of increased intracranial pressure: 101 patients with benign intracranial hypertension. Neurology. 1988;38:1461-1464. 31. Kuensting LL. A 15-year-old with blurred vision, nausea, back pain, and abdominal pain. J Emerg Nurs. 2003;29:171-173.
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32. Lessell S. Pediatric pseudotumor cerebri (idiopathic intracranial hypertension). Surv Ophthalmol. 1992;37:155-166. 33. Jacks AS, Miller NR. Spontaneous retinal venous pulsation: Aetiology and significance. J Neurol Neurosurg Psychiatry. 2003;74:7-9. 34. Jonas JB. The effect of optic disk edema on spontaneous venous pulsations. Am J Ophthalmol. 2003;136:1196. 35. McKee HD, Ahad MA. Spontaneous retinal venous pulsations can be present with a swollen optic disc. J Neurol Neurosurg Psychiatry. 2004;75:941. 36. Walsh TJ, Garden JW, Gallagher B. Obliteration of retinal venous pulsations during elevation of cerebrospinal-fluid pressure. Am J Ophthalmol. 1969;67:954-956. 37. Sedwick LA, Burde RM. Unilateral and asymmetric optic disk swelling with intracranial abnormalities. Am J Ophthalmol. 1983; 96:484-487. 38. Hayreh MS, Hayreh SS. Optic disc edema in raised intracranial pressure. I. Evolution and resolution. Arch Ophthalmol. 1977;95: 1237-1244. 39. Hayreh SS. Optic disc edema in raised intracranial pressure. V. Pathogenesis. Arch Ophthalmol. 1977;95:1553-1565. 40. Hayreh SS, Hayreh MS. Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography. Arch Ophthalmol. 1977;95: 1245-1254. 41. Tso MO, Hayreh SS. Optic disc edema in raised intracranial pressure. III. A pathologic study of experimental papilledema. Arch Ophthalmol. 1977;95:1448-1457. 42. Tso MO, Hayreh SS. Optic disc edema in raised intracranial pressure. IV. Axoplasmic transport in experimental papilledema. Arch Ophthalmol. 1977;95:1458-1462. 43. Maxner CE, Freedman MI, Corbett JJ. Asymmetric papilledema and visual loss in pseudotumour cerebri. Can J Neurol Sci. 1987;14:593-596. 44. Thurtell MJ, Newman NJ, Biousse V. Visual loss without papilledema in idiopathic intracranial hypertension. J Neuroophthalmol. 2010;30:96-98. 45. Peng KP, Fuh JL, Wang SJ. High-pressure headaches: Idiopathic intracranial hypertension and its mimics. Nat Rev Neurol. 2012;8:700-710. 46. Nguyen C, Borruat FX. Bilateral peripapillary subretinal neovessel membrane associated with chronic papilledema: Report of two cases. Klin Monatsbl Augenheilkd. 2005;222:275-278. 47. Pilon A, Newman T, Messner LV. Neurosensory detachment arising from a fractured inner-limiting membrane secondary to chronically elevated intraocular pressure. Optom Vis Sci. 2006;83:415-420. 48. Sathornsumetee B, Webb A, Hill DL, Newman NJ, Biousse V. Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. J Neuroophthalmol. 2006;26:197-199. 49. Shah VA, Kardon RH, Lee AG, Corbett JJ, Wall M. Long-term follow-up of idiopathic intracranial hypertension: The Iowa experience. Neurology. 2008;70:634-640. 50. Tyson SL, Lessell S. Resolution of optociliary shunt vessels. J Clin Neuroophthalmol. 1986;6:205-208.
Headache Currents 51. Corbett JJ, Savino PJ, Thompson HS, et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol. 1982;39:461-474. 52. Kupersmith MJ, Sibony P, Mandel G, Durbin M, Kardon RH. Optical coherence tomography of the swollen optic nerve head: Deformation of the peripapillary retinal pigment epithelium layer in papilledema. Invest Ophthalmol Vis Sci. 2011;52:65586564. 53. Skau M, Milea D, Sander B, Wegener M, Jensen R. OCT for optic disc evaluation in idiopathic intracranial hypertension. Graefes Arch Clin Exp Ophthalmol. 2011;249:723-730. 54. Sibony P, Kupersmith MJ, Rohlf FJ. Shape analysis of the peripapillary RPE layer in papilledema and ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2011;52:7987-7995. 55. Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008;8:87-93. 56. Celebisoy N, Gokcay F, Sirin H, Akyurekli O. Treatment of idiopathic intracranial hypertension: Topiramate vs acetazolamide, an open-label study. Acta Neurol Scand. 2007;116:322-327. 57. Pagan FL, Restrepo L, Balish M, Patwa HS, Houff S. A new drug for an old condition? Headache. 2002;42:695-696. 58. Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology. 1998; 105:2313-2317. 59. Liu GT, Glaser JS, Schatz NJ. High-dose methylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J Ophthalmol. 1994;118:88-96. 60. Ahmed R, Friedman DI, Halmagyi GM. Stenting of the transverse sinuses in idiopathic intracranial hypertension. J Neuroophthalmol. 2011;31:374-380. 61. Rosenberg ML, Corbett JJ, Smith C, et al. Cerebrospinal fluid diversion procedures in pseudotumor cerebri. Neurology. 1993;43: 1071-1072. 62. Acheson JF, Green WT, Sanders MD. Optic nerve sheath decompression for the treatment of visual failure in chronic raised intracranial pressure. J Neurol Neurosurg Psychiatry. 1994;57:14261429. 63. Banta JT, Farris BK. Pseudotumor cerebri and optic nerve sheath decompression. Ophthalmology. 2000;107:1907-1912. 64. Horton JC, Seiff SR, Pitts LH, Weinstein PR, Rosenblum ML, Hoyt WF. Decompression of the optic nerve sheath for visionthreatening papilledema caused by dural sinus occlusion. Neurosurgery. 1992;31:203-211; discussion 11-2. 65. Nithyanandam S, Manayath GJ, Battu RR. Optic nerve sheath decompression for visual loss in intracranial hypertension: Report from a tertiary care center in South India. Indian J Ophthalmol. 2008;56:115-120. 66. Sergott RC. Optic nerve sheath decompression: History, techniques, and indications. Int Ophthalmol Clin. 1991;31:71-81. 67. Uretsky S. Surgical interventions for idiopathic intracranial hypertension. Curr Opin Ophthalmol. 2009;20:451-455. 68. Plotnik JL, Kosmorsky GS. Operative complications of optic nerve sheath decompression. Ophthalmology. 1993;100:683-690.
HEADACHE CURRENTS—CLINICAL REVIEW
Idiopathic Intracranial Hypertension: Pseudotumor Cerebri Gregory S. Kosmorsky, DO
Background.—Idiopathic intracranial hypertension (IIH) is most often diagnosed in young obese females of childbearing years. The diagnosis is made based on the modified Dandy criteria and the exclusion of alternate causes of raised intracranial pressure. Results.—The focus of this review is to provide an overview of the diagnosis and treatment options for patients with IIH. There are long-term consequences for patients experiencing IIH, with visual loss being the most serious. Conclusion.—We conclude that the diagnosis of IIH is not usually difficult. An ophthalmologic examination is essential in patients with IIH to monitor visual function. A neurologist or neurosurgeon may be needed at some point for medical and/or surgical intervention. Key words: idiopathic intracranial hypertension, pseudotumor cerebri, cerebrospinal fluid, increased cerebrospinal fluid pressure, Dandy criteria
Idiopathic intracranial hypertension (IIH) is a disorder generally affecting overweight women of childbearing years.1-4 The pathogenesis is unknown, but ultimately, a defect in water absorption seems to be the common feature. Although it is believed that this absorptive problem occurs at the level of the arachnoid,5 recent insights into the water balance of the brain challenge this contention.6 The diagnosis is based on clinical symptomatology and findings, normal imaging studies, an elevated opening pressure on lumbar puncture with a normal cerebrospinal fluid (CSF) constituency, and elimination of systemic disorders that mimic the typical profile.7 The modified Dandy criteria serve as the basis for the diagnosis and include: (1) symptoms and signs of increased intracranial pressure (ICP); (2) no localizing neurologic signs, except for unilateral or bilateral sixth nerve palsies; (3) increased CSF opening pressure, but normal CSF constituency; (4) no evidence of hydrocephalus, mass, structural, or vascular lesion on imaging; and (5) no other cause of increased ICP identified.8
IIH Clinical Characteristics The patient profile in IIH is quite striking and characteristic. Overwhelmingly, this is a disorder of overweight females of From the Cole Eye Institute, Cleveland, OH, USA. Address all correspondence to Gregory S. Kosmorsky, Cleveland Clinic Foundation, Cole Eye Institute, Cleveland Clinic I-30, Cleveland, OH 44195, USA. Accepted for publication October 25, 2013. ............. Headache © 2014 American Headache Society
childbearing years. It is the most skewed non-sex organ–related disorder, with a female to male ratio of 9:1.3 The most common manifestation of IIH is headache. This has been reported in 75-99% of patients. The headache is non-specific and is usually holocranial although it can be vertex or suboccipital. Similar to all headaches due to elevated ICP, it may be worse upon awakening and increased with the Valsalva maneuver. It should be noted that as many as 10% of patients with IIH are entirely asymptomatic from a headache perspective.9,10 The headache can be severe and does seem to negatively impact quality-of-life indicators as measured by the HRQOL score.3 Monocular and binocular transient visual obscurations (TVOs) are momentary blackouts of vision most likely due to temporary disruption in the microcirculation of the optic nerve head induced by transient changes in perfusion pressure at the level of the optic nerve usually associated with postural changes. Many TVOs occur with a postural change, although some may occur while the patient sits quietly. TVOs are not predictive of permanent visual loss and can disappear with or without a reduction in CSF pressure.1,11 They are not unique to IIH and have been shown to occur with any disorder that produces swelling of the optic nerve head. Sadun et al have demonstrated that TVOs may occur in patients with elevated optic discs from causes not related to increased ICP.12 They postulate that these visual obscurations appear to be due to transient ischemia of the optic nerve head consequent to increased tissue pressure within the optic nerve. They further postulate that axonal swelling, intraneural masses, and increased influx of interstitial fluid may all contribute to increases in tissue pressure in the optic nerve head, consequently reducing the perfusion pressure in the small, low-pressure vessels that supply the optic nerve. Even disorders such as myopia and optic nerve drusen have produced TVOs. Evaluation and Workup The evaluation of IIH includes the history, physical examination, blood work, imaging studies, and a lumbar puncture. The history and physical should suggest raised ICP. Mimickers such as cerebral venous thrombosis, gliomatosis cerebri, and leptomeningeal infiltration by neoplastic or infectious processes need to be considered. A complete blood count (CBC) and general chemistry analysis should be obtained to exclude anemia or lymphoproliferative causes. The general chemistry can be used to detect renal disease that can complicate this condition especially in African American males.13 Iron deficiency can be reflected in the CBC; therefore, iron studies could be ordered when indicated. ............. The author has no conflicts to disclose.
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Imaging studies are mandatory and the MRI is the preferred modality given its ability to not only detects mass lesions and hydrocephalus, but also to detect venous sinus thrombosis and potentially a meningeal process. A lumbar puncture is required to establish the level of CSF pressure and to examine the CSF constituency.14,15 Red flags in the diagnosis of IIH include: (1) atypical demographic profile; (2) cranial nerve palsies other than a 6th nerve palsy; (3) alterations in level of consciousness; (4) focal neurologic sings apart from a 6th nerve palsy; (5) abnormal CSF profile; (6) explosive onset of symptoms; (7) rapid development of visual loss and progression of symptoms; (8) global ophthalmoplegia; (9) internuclear ophthalmoplegia; and (10) vertical gaze disorder.14 Further Clinical Features in Considering the Diagnosis Diplopia occurs almost exclusively from 6th nerve palsies16 that may be unilateral or bilateral and are non-localizing. There are rare reports of skew deviation,17 4th nerve palsies,18,19 and even 3rd nerve palsies in IIH;20,21 however, these occurrences are exceptional, and the diagnosis was not firm in some of these patients. Any diplopia not due to a 6th nerve palsy should make the diagnosis of IIH suspect. Facial paresis and facial pain have occasionally been reported in IIH.22-26 These are extremely unusual features, and mass lesions should be ruled out in these patients. Pulsatile tinnitus due to elevated ICP is most likely the result of turbulent blood flow at the level of the jugular bulb during diastole wherein elevated CSF pressure causes these draining veins to vibrate.27-29 Tinnitus due to elevated ICP can be differentiated from tinnitus due to other causes by reducing CSF pressure via a lumbar puncture or compression of the internal jugular vein that prevents the jugular vein from vibrating during diastole. Low back pain and radiating paresthesias are thought to be due to dilation of nerve root sleeves secondary to increased ICP.30 Paresthesias in IIH have been reported in all extremities and without demonstrable sensory abnormalities. Aching legs can be a complaint with IIH and may be attributed to pressure on the lumbar roots at the level of the dural sleeve.31,32 Arthralgia coincided with high-pressure plateau waves during continuous ICP monitoring in a patient with “high pressure normocephalus.” This patient had episodic pain of the shoulders, knees, and hips, with headache as a minor complaint.30 Momentary ataxia occurred in four patients in the report of Round and Keane, who suggested that this may be due to brief hypoperfusion of the brain stem.30 Papilledema in IIH is no different from papilledema in any other condition related to increased ICP. Swelling of the nerve fiber layer occurs, with hemorrhages in the nerve fiber layer or in the subretinal space being frequently seen. Lipoproteinaceous exudates within the retina, as well as cotton-wool spots from infarction of the nerve fiber layer, may be
Headache Currents seen, but these other features may suggest other disorders, particularly vasculitis. Loss of venous pulsations is typical with increasing ICP, although spontaneous venous pulsations may be seen in patients with papilledema, indicating that the ICP at that time may in fact be normal or that SVPs may still be present with increased ICP in some patients.33-36 There is no direct correlation of the presence of venous pulsations and level of ICP. Predominantly unilateral or strictly unilateral optic nerve swelling has occasionally been reported.37 The presence of highly asymmetric or strictly unilateral papilledema should not dissuade a physician from making the diagnosis of IIH. Asymmetric papilledema is thought to be due to differences in individual optic nerve anatomy as shown by Hayreh et al.38-42 Hayreh demonstrated in pathologic specimens that some individuals have a tighter subarachnoid space within the optic canal, thereby preventing raised ICP from accessing the posterior globe at the lamina cribrosa, where either mechanical and/or ischemic factors seem to produce papilledema. Such a patient was described by Maxner et al in whom unilateral papilledema in the left eye led to an initial diagnosis of anterior ischemic optic neuropathy.43 Gradual progression of visual field loss prompted reassessment, with the eventual diagnosis of IIH being confirmed. Even more unusual is the absence of papilledema with raised ICP.44 Such cases are considered rare; however, because clinicians do not routinely do lumbar punctures on patients without papilledema, the true incidence of this presentation is likely underestimated. In patients diagnosed with chronic daily headache (without papilledema), the proportion of patients with IIH seems to be higher.45 Although most patients present with mild to moderate grades of papilledema, there are those who present with a very aggressive form of IIH with severe papilledema and profound visual loss. These patients require aggressive treatment and my approach is to try medications (acetazolamide and burst and taper methylprednisolone) for a short period of time (1-2 weeks), and if the visual loss is not quickly reversed, I proceed to optic nerve sheath fenestration or refer to neurosurgery for a ventriculoperitoneal shunt. It is impossible to ascertain how long papilledema has been present merely by fundus appearance. Papilledema of long standing may appear to be quite new, with hyperemia of the disc and telangiectatic-like dilation of the capillaries on the surface of the disc. However, if optic atrophy, gliosis, optociliary shunts, and pseudodrusen (tiny reflectile particles in the nerve fiber layer) are seen, chronicity may be implied, although the exact length of time is impossible to ascertain. Papilledema may resolve with little or no residuum. Consequences of sustained increases of ICP include optic atrophy with or without significant visual loss, optociliary shunt vessels, chorioretinal folds, subretinal hemorrhages, macular
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edema, peripapillary choroidal neovascular membranes, and nerve fiber layer defects with visual field loss.46-50 Chronic papilledema may also cause arterial or venous occlusions (either total or partial), presumably on the basis of mechanical distortion of the arteries or veins. Long-Term Consequences of IIH Visual field abnormalities in IIH are common and occur in approximately 50% of patients.49,51 Serious unilateral or bilateral visual loss has been reported in up to 25% of patients. It is generally agreed that visual loss is the only serious complication of IIH. The most common visual field defect is an enlarged blind spot that has been shown to be secondary to a refractive scotoma, presumably due to displacement of the peripapillary rods and cones by swollen axons.43 Because blind spot enlargement may persist after papilledema disappears and because other conditions mimicking papilledema, such as drusen, can also enlarge the blind spot, plotting the blind spot is an unreliable measure of therapeutic success and an inaccurate way of observing a patient’s visual function. Rather, arcuate or altitudinal defects that indicate affectation of the nerve fiber layer are more consequential and indicative of optic nerve dysfunction. As with glaucoma, central acuity is lost last in papilledema, and assessment of the visual field with formal testing is mandatory in this disorder to assure proper function of the optic nerve. Generalized constriction of the visual field may be seen in papilledema and indicates severe loss of the nerve fiber layer. However, this is a non-specific sign and may be seen with abnormalities of the cornea or lens or simply with inattention during the testing process, as well as many other factors. Nerve fiber layer defects are common in IIH. These are usually arcuate scotomas in the nasal region and may be either inferior or superior and identical to those field defects seen in any type of optic neuropathy. Even altitudinal visual field-shaped defects or temporal visual field defects can be seen. Central visual field loss is not common but may occur with involvement of the papillomacular bundle and as noted above, usually a late finding. Central visual field loss may also result from subretinal hemorrhage within the papillomacular bundle or macula, secondary to significant papilledema. Assessment of the nerve fiber layer has been greatly enhanced with the use of ocular coherence tomography (OCT) that can reliable measure the thickness of the retina and give a repeatable and statistically valid representation of the degree of injury to the optic nerve.52,53 OCT may be used to differentiate swelling from raised ICP from ischemic optic neuropathy.54 Since patients with functional disease present to the clinician, we should be wary of patients claiming severe visual loss in the absence of papilledema or optic atrophy. The pathophysiology of the visual loss requires the optic disc to be swollen, as the axons of the optic nerve cannot be damaged by raised ICP anywhere
Headache Currents except at the neuro-ocular junction (in the same way that the neurons of the brain tolerate the raised ICP without becoming edematous). The relative afferent pupillary defect (RAPD) is an objective sign of anterior visual pathway dysfunction. Papilledema may cause temporary or permanent dysfunction of visual axons. If this damage is asymmetric, the RAPD will become apparent clinically. Symmetric dysfunction will not produce an RAPD, despite significant visual loss. The finding of an RAPD is extremely important because it indicates the need for intervention in a patient with IIH. Management of IIH Treatment of the visual aspects of IIH depends on the severity of the disorder. Since many patients have little if any visual field loss, no particular therapy is required in the face of a normal visual field. Headache in the setting of a normal visual field may represent a sufficient reason for treatment. In those patients with significant initial field loss, or particularly in those with progressive visual field loss, treatment with medications that lower ICP is indicated. Acetazolamide has been demonstrated to be the most potent medication for lowering ICP.8,55 The usual dosage is either 500 mg sequels bid or 250 mg tablets qid. The branded DIAMOX sequels are significantly more expensive than the generic tablet form. Other sulfa-containing compounds such as furosemide and topiramate may also be used, as drugs in this class all interfere with carbonic anhydrase and reduce the amount of CSF that is made, bringing CSF production into line with reduced CSF drainage. Topiramate has the added advantage of blocking the upregulation of pain signaling and therefore can address both the CSF production and headache aspects.55-57 Weight loss of as little as 6% of body weight has been shown to reduce papilledema, and this form of therapy should be encouraged.58 Pulsed corticosteroids have been demonstrated to have an ameliorating effect, but long-term use of steroids should be avoided.59 A controversial approach is to employ venous stenting procedures to reduce the ICP. Narrowing of the draining veins has been proposed as a mechanism of raised ICP, but it may be that the elevation of ICP causes the narrowing.60 If medications and weight loss fail, some form of CSF diversion procedure would be indicated. The neurosurgical approach usually involves either and lumboperitoneal shunt or ventriculoperitoneal shunt, but other procedures have been described.11,61 From an ophthalmic perspective, optic nerve sheath decompression (ONSD) is the primary procedure.62-67 This procedure may be performed from either the medial, lateral, or superior approach. I prefer the medial approach because it is rapid and
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opens the dura/arachnoid complex on the nasal side avoiding the papillomacular bundle that is temporally situated, if the knife were to penetrate too deeply with the lateral approach. The superior approach is preferred by some ophthalmic plastic surgeons, but the majority of surgeons performing ONSD prefer the medial approach. The purpose of the procedure is to divert elevated CSF pressure that is transmitted from the CSF compartment to the neuroocular junction via the subarachnoid space of the optic nerve that is continuous with the CSF compartment. The CSF then leaks into the periorbital fat via the formation of a filtration bleb and is absorbed by the veins in the fat. Although ONSD can be very effective, it can result in a range of complications.68
SUMMARY The diagnosis of IIH is usually not difficult. Provided that the history, examination, neuroimaging studies, and lumbar puncture are all consistent with IIH, the diagnosis can be made easily. The elimination of look-alikes should be complete with appropriate testing. After the diagnosis is made, patients should be observed closely in terms of their visual field and visual acuity until it is apparent that these are stable. Patients who have progressive loss of visual acuity or visual field should be treated promptly. An ophthalmologist should be involved in the care of these patients along with a neurologist or neurosurgeon because visual loss may occur either early or late in the disease process and may be insidious. The most effective treatments are weight loss, carbonic anhydrase inhibitors, and diuretics, and, if necessary, a short course of steroids. If visual loss occurs despite these maneuvers, some type of shunt procedure is recommended. There seems to be no reason to treat the asymptomatic patient with IIH. References 1. Corbett J. Idiopathic intracranial hypertension. J Neuroophthalmol. 2012;32:e4-e6. 2. Corbett JJ. The 1982 silversides lecture. Problems in the diagnosis and treatment of pseudotumor cerebri. Can J Neurol Sci. 1983;10: 221-229. 3. Daniels AB, Liu GT, Volpe NJ, et al. Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri). Am J Ophthalmol. 2007;143:635-641. 4. Durcan FJ, Corbett JJ, Wall M. The incidence of pseudotumor cerebri. Population studies in Iowa and Louisiana. Arch Neurol. 1988;45:875-877. 5. Johnston I, Paterson A. Benign intracranial hypertension. II. CSF pressure and circulation. Brain. 1974;97:301-312. 6. Oreskovic D, Klarica M. The formation of cerebrospinal fluid: Nearly a hundred years of interpretations and misinterpretations. Brain Res Rev. 2010;64:241-262. 7. Friedman DI. Idiopathic intracranial hypertension with Dan and beyond: The 2010 Jacobson Lecture. J Neuroophthalmol. 2010;30: 380-385.
Headache Currents 8. Thurtell MJ, Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri): Recognition, treatment, and ongoing management. Curr Treat Options Neurol. 2013;15:1-12. 9. Strominger MB, Weiss GB, Mehler MF. Asymptomatic unilateral papilledema in pseudotumor cerebri. J Clin Neuroophthalmol. 1992;12:238-241. 10. Weig SG. Asymptomatic idiopathic intracranial hypertension in young children. J Child Neurol. 2002;17:239-241. 11. Corbett JJ, Thompson HS. The rational management of idiopathic intracranial hypertension. Arch Neurol. 1989;46:1049-1051. 12. Sadun AA, Currie JN, Lessell S. Transient visual obscurations with elevated optic discs. Ann Neurol. 1984;16:489-494. 13. Corbett JJ. Increased intracranial pressure: Idiopathic and otherwise. J Neuroophthalmol. 2004;24:103-105. 14. Friedman DI, Jacobson DM. Idiopathic intracranial hypertension. J Neuroophthalmol. 2004;24:138-145. 15. Kosmorsky G. Pseudotumor cerebri. Neurosurg Clin N Am. 2001;12:775-797, ix. 16. Bruce BB, Newman NJ, Biousse V. Ophthalmoparesis in idiopathic intracranial hypertension. Am J Ophthalmol. 2006;142:878-880. 17. Baker RS, Buncic JR. Vertical ocular motility disturbance in pseudotumor cerebri. J Clin Neuroophthalmol. 1985;5:41-44. 18. Lee AG. Fourth nerve palsy in pseudotumor cerebri. Strabismus. 1995;3:57-59. 19. Speer C, Pearlman J, Phillips PH, Cooney M, Repka MX. Fourth cranial nerve palsy in pediatric patients with pseudotumor cerebri. Am J Ophthalmol. 1999;127:236-237. 20. Tan H. Bilateral oculomotor palsy secondary to pseudotumor cerebri. Pediatr Neurol. 2010;42:141-142. 21. Thapa R, Mukherjee S. Transient bilateral oculomotor palsy in pseudotumor cerebri. J Child Neurol. 2008;23:580-581. 22. Bakshi SK, Oak JL, Chawla KP, Kulkarni SD, Apte N. Facial nerve involvement in pseudotumor cerebri. J Postgrad Med. 1992;38:144145. 23. Kearsey C, Fernando P, Benamer HT, Buch H. Seventh nerve palsy as a false localizing sign in benign intracranial hypertension. J R Soc Med. 2010;103:412-414. 24. Capobianco DJ, Brazis PW, Cheshire WP. Idiopathic intracranial hypertension and seventh nerve palsy. Headache. 1997;37:286288. 25. Chutorian AM, Gold AP, Braun CW. Benign intracranial hypertension and Bell’s palsy. N Engl J Med. 1977;296:1214-1215. 26. Kiwak KJ, Levine SE. Benign intracranial hypertension and facial diplegia. Arch Neurol. 1984;41:787-788. 27. Lee AG. Pulsatile tinnitus as a presenting symptom of pseudotumour cerebri. J Otolaryngol. 1996;25:203-204. 28. Sismanis A. Otologic manifestations of benign intracranial hypertension syndrome: Diagnosis and management. Laryngoscope. 1987;97(8 Pt 2 Suppl. 42):1-17. 29. Sismanis A. Pulsatile tinnitus. A 15-year experience. Am J Otol. 1998;19:472-477. 30. Round R, Keane JR. The minor symptoms of increased intracranial pressure: 101 patients with benign intracranial hypertension. Neurology. 1988;38:1461-1464. 31. Kuensting LL. A 15-year-old with blurred vision, nausea, back pain, and abdominal pain. J Emerg Nurs. 2003;29:171-173.
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32. Lessell S. Pediatric pseudotumor cerebri (idiopathic intracranial hypertension). Surv Ophthalmol. 1992;37:155-166. 33. Jacks AS, Miller NR. Spontaneous retinal venous pulsation: Aetiology and significance. J Neurol Neurosurg Psychiatry. 2003;74:7-9. 34. Jonas JB. The effect of optic disk edema on spontaneous venous pulsations. Am J Ophthalmol. 2003;136:1196. 35. McKee HD, Ahad MA. Spontaneous retinal venous pulsations can be present with a swollen optic disc. J Neurol Neurosurg Psychiatry. 2004;75:941. 36. Walsh TJ, Garden JW, Gallagher B. Obliteration of retinal venous pulsations during elevation of cerebrospinal-fluid pressure. Am J Ophthalmol. 1969;67:954-956. 37. Sedwick LA, Burde RM. Unilateral and asymmetric optic disk swelling with intracranial abnormalities. Am J Ophthalmol. 1983; 96:484-487. 38. Hayreh MS, Hayreh SS. Optic disc edema in raised intracranial pressure. I. Evolution and resolution. Arch Ophthalmol. 1977;95: 1237-1244. 39. Hayreh SS. Optic disc edema in raised intracranial pressure. V. Pathogenesis. Arch Ophthalmol. 1977;95:1553-1565. 40. Hayreh SS, Hayreh MS. Optic disc edema in raised intracranial pressure. II. Early detection with fluorescein fundus angiography and stereoscopic color photography. Arch Ophthalmol. 1977;95: 1245-1254. 41. Tso MO, Hayreh SS. Optic disc edema in raised intracranial pressure. III. A pathologic study of experimental papilledema. Arch Ophthalmol. 1977;95:1448-1457. 42. Tso MO, Hayreh SS. Optic disc edema in raised intracranial pressure. IV. Axoplasmic transport in experimental papilledema. Arch Ophthalmol. 1977;95:1458-1462. 43. Maxner CE, Freedman MI, Corbett JJ. Asymmetric papilledema and visual loss in pseudotumour cerebri. Can J Neurol Sci. 1987;14:593-596. 44. Thurtell MJ, Newman NJ, Biousse V. Visual loss without papilledema in idiopathic intracranial hypertension. J Neuroophthalmol. 2010;30:96-98. 45. Peng KP, Fuh JL, Wang SJ. High-pressure headaches: Idiopathic intracranial hypertension and its mimics. Nat Rev Neurol. 2012;8:700-710. 46. Nguyen C, Borruat FX. Bilateral peripapillary subretinal neovessel membrane associated with chronic papilledema: Report of two cases. Klin Monatsbl Augenheilkd. 2005;222:275-278. 47. Pilon A, Newman T, Messner LV. Neurosensory detachment arising from a fractured inner-limiting membrane secondary to chronically elevated intraocular pressure. Optom Vis Sci. 2006;83:415-420. 48. Sathornsumetee B, Webb A, Hill DL, Newman NJ, Biousse V. Subretinal hemorrhage from a peripapillary choroidal neovascular membrane in papilledema caused by idiopathic intracranial hypertension. J Neuroophthalmol. 2006;26:197-199. 49. Shah VA, Kardon RH, Lee AG, Corbett JJ, Wall M. Long-term follow-up of idiopathic intracranial hypertension: The Iowa experience. Neurology. 2008;70:634-640. 50. Tyson SL, Lessell S. Resolution of optociliary shunt vessels. J Clin Neuroophthalmol. 1986;6:205-208.
Headache Currents 51. Corbett JJ, Savino PJ, Thompson HS, et al. Visual loss in pseudotumor cerebri. Follow-up of 57 patients from five to 41 years and a profile of 14 patients with permanent severe visual loss. Arch Neurol. 1982;39:461-474. 52. Kupersmith MJ, Sibony P, Mandel G, Durbin M, Kardon RH. Optical coherence tomography of the swollen optic nerve head: Deformation of the peripapillary retinal pigment epithelium layer in papilledema. Invest Ophthalmol Vis Sci. 2011;52:65586564. 53. Skau M, Milea D, Sander B, Wegener M, Jensen R. OCT for optic disc evaluation in idiopathic intracranial hypertension. Graefes Arch Clin Exp Ophthalmol. 2011;249:723-730. 54. Sibony P, Kupersmith MJ, Rohlf FJ. Shape analysis of the peripapillary RPE layer in papilledema and ischemic optic neuropathy. Invest Ophthalmol Vis Sci. 2011;52:7987-7995. 55. Wall M. Idiopathic intracranial hypertension (pseudotumor cerebri). Curr Neurol Neurosci Rep. 2008;8:87-93. 56. Celebisoy N, Gokcay F, Sirin H, Akyurekli O. Treatment of idiopathic intracranial hypertension: Topiramate vs acetazolamide, an open-label study. Acta Neurol Scand. 2007;116:322-327. 57. Pagan FL, Restrepo L, Balish M, Patwa HS, Houff S. A new drug for an old condition? Headache. 2002;42:695-696. 58. Johnson LN, Krohel GB, Madsen RW, March GA Jr. The role of weight loss and acetazolamide in the treatment of idiopathic intracranial hypertension (pseudotumor cerebri). Ophthalmology. 1998; 105:2313-2317. 59. Liu GT, Glaser JS, Schatz NJ. High-dose methylprednisolone and acetazolamide for visual loss in pseudotumor cerebri. Am J Ophthalmol. 1994;118:88-96. 60. Ahmed R, Friedman DI, Halmagyi GM. Stenting of the transverse sinuses in idiopathic intracranial hypertension. J Neuroophthalmol. 2011;31:374-380. 61. Rosenberg ML, Corbett JJ, Smith C, et al. Cerebrospinal fluid diversion procedures in pseudotumor cerebri. Neurology. 1993;43: 1071-1072. 62. Acheson JF, Green WT, Sanders MD. Optic nerve sheath decompression for the treatment of visual failure in chronic raised intracranial pressure. J Neurol Neurosurg Psychiatry. 1994;57:14261429. 63. Banta JT, Farris BK. Pseudotumor cerebri and optic nerve sheath decompression. Ophthalmology. 2000;107:1907-1912. 64. Horton JC, Seiff SR, Pitts LH, Weinstein PR, Rosenblum ML, Hoyt WF. Decompression of the optic nerve sheath for visionthreatening papilledema caused by dural sinus occlusion. Neurosurgery. 1992;31:203-211; discussion 11-2. 65. Nithyanandam S, Manayath GJ, Battu RR. Optic nerve sheath decompression for visual loss in intracranial hypertension: Report from a tertiary care center in South India. Indian J Ophthalmol. 2008;56:115-120. 66. Sergott RC. Optic nerve sheath decompression: History, techniques, and indications. Int Ophthalmol Clin. 1991;31:71-81. 67. Uretsky S. Surgical interventions for idiopathic intracranial hypertension. Curr Opin Ophthalmol. 2009;20:451-455. 68. Plotnik JL, Kosmorsky GS. Operative complications of optic nerve sheath decompression. Ophthalmology. 1993;100:683-690.
